This renewal proposal comprises 2 parts in our ongoing gallstone program. Part I, the major thrust of this 4 year request, concerns further study in our hamster model of the hepatic and biliary effects of agents that may be useful for gallstone dissolution in man. Part II is a 1 year request to complete our "double blind" evaluation of the efficacy, safety and mechanisms of action of chenodeoxycholic acid, phenobarbital, both or placebo in gallstone dissolution in man. Bile that contains more cholesterol than can be solubilized by bile acid and phospholipid leads to precipitation of cholesterol crystals and formation of cholesterol gallstones. Chenodeoxycholic acid (CDC) has been reported to reverse this defect and dissolve gallstones. Data is not available in humans or animals that defines the most effective and safe dose regime for chenodeoxycholic acid or other agents in gallstone dissolution. Furthermore, toxicity studies in animals suggest that chenodeoxycholic acid may cause a dose related hepatic injury but the mechanism is not known. Part I is a study in the hamster of the magnitude, sequence and duration of action of graded daily and alternate-day doses of chenodeoxycholic acid and of other agents including phenobarbital and thyroid hormone. The objectives are to identify potentially effective dose regimes and mechanisms of hepatic toxicity. Biliary and hepatic lipid and bile acid composition, liver morphology and the hepatic rate limiting enzymes for cholesterol synthesis (HMG Co A reductase) and bile acid synthesis (7 alpha hydroxylase) will be determined.